[Frontiers In Bioscience, Landmark, 23, 1310-1319, January 1, 2018]

A role of LINE-1 in telomere regulation

Catharina Mueller1, Thomas Aschacher1, Brigitte Wolf1, Michael Bergmann1,2,

1Surgical Research Laboratories, Dept. of Surgery, 2Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria

TABLE OF CONTENTS

1. Abstract
2. Introduction
2.1. Evidence for multiple functions of LINE-1
2.2. Telomere structure and function
3. LINE-1 and telomeres
3.1. Effect of LINE-1 on telomere maintenance mechanism
3.2. Evolutionary aspects
3.3. Implications for stem cells and embryogenesis
3.4. Therapeutic implications
4. Acknowledgements
5. References

1. ABSTRACT

Long interspersed nuclear elements (LINE-1) are well known as retrotransposons. A number of reports indicate that down-regulation of LINE-1 substantially affects growth of malignant cells and epithelial mesenchymal transition, which is difficult to be explained by its function as retrotransposon. More recent data indicate that LINE-1 is broadly involved in the regulation of telomere maintenance. This explains the essential role of LINE-1 for survival of malignant cells and further supports a global function of active LINE-1 elements in cell proliferation. We further discuss the implications of LINE-1-associated telomere regulation on evolution of telomeric structures, on embryogenesis and on therapy of malignancies.

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Abbreviations: LINE-1: long interspersed nuclear element; LTR: long terminal repeat; RT: reverse transcriptase, EMT: epithelial mesenchymal transition; TMM: telomere maintenance mechanism; DDR: DNA damage response; ATM: ataxia telangiectasia mutated kinase; ATR: ataxia telangiectasia and Rad3 related kinase; hTERT: human telomerase; TA: telomerase activity; ALT: alternative lengthening of telomeres; APB: ALT-associated promyelocytic leukemia bodies; TERRA: telomeric repeat containing RNA; RPA: replication binding protein A; HR: homologous recombination; TIF: telomere induced foci; KD: knock down; NHEJ: non-homologous end joining; RTI: reverse transcriptase inhibitor; N-RTI: nucleotide-analogue RTI; NN-RTI: non nucleotide-analogue RTI.

Key Words: Telomere, LINE-1, Shelterin, Telomerase, Retrotransposon, Reverse Transciptase Inhibitors, Review

Send correspondence to: Michael Bergmann, Dept. of Surgery, Medical University of Vienna, Waehringer Gurtel 18-20, 1090 Vienna, Austria, Tel: 43 1 40400 69590, Fax: 43 1 40400 67820, E-mail: michael.bergmann@meduniwien.ac.at